Peer victimization is a salient form of early adversity with long-term costs for youths' mental health. Indeed, research and media coverage place peer victimization on the national agenda as a critical public health issue, given its prevalence and it implications for emotional well-being into adolescence and adulthood. Identifying processes accounting for these enduring effects is critical for informing policy and practice, yet scientists have not yet discovered the processes through which victimization derails youths' development-that is, how victimization gets under the skin in ways that instill long-term risk. Inspired by a growing recognition of the pervasive impact of early life stress on maturing brain systems and associated psychopathology, this research will contribute substantially to scientific knowledge and its application by documenting the adolescent sequelae of victimization, with broader implications for enriching our understanding of the mechanisms through which early adversity shapes stress reactivity and mental health. Integrating ideas across the fields of developmental and social psychology, social affective neuroscience, and developmental psychopathology with the NIMH RDoC framework, this research will examine whether victimization is linked to dysregulated negative valence systems involved in sustained threat/loss, thereby heightening reactivity and compromising regulation and contributing to adolescent depression. Introducing an innovative methodological approach into the field of peer victimization, this research will use a multi-level design, examining reactivity and regulation at both the neural and behavioral levels in the context of an experimental design (laboratory cues of social threat/loss). This study will take advantage of an existing sample of adolescent girls (10th-11th graders), well-characterized on victimization, individual differences in risks and resources, and mental health from 2nd-9th grade, thereby providing the opportunity to leverage a comprehensive longitudinal data set to enrich the proposed short-term (two-year) investigation of neural/behavioral processing and depressive symptoms. Thus, this study is uniquely positioned to examine the link between childhood victimization and subsequent neural and behavioral processing of social cues as well as to determine whether stress reactivity/regulation account for the contribution of victimization to adolescent depression. This research also will provide novel data on individual differences in risk and resilience processes, thereby maximizing the efficiency of prevention/intervention programs. Ultimately, it is anticipated that this researc will serve as a basis for larger longitudinal studies investigating: (a) how early adversity withina variety of contexts influences emerging brain systems in ways that set the stage for adolescent mental health problems; and (b) individual and contextual resources that may buffer youth against these adverse consequences. This line of research can yield clear and compelling implications for policy and practice guidelines aimed at minimizing the threat posed by early social adversity to youths' health and development, with potential implications for long-term adaptation and societal burden.